Proteus syndrome is a rare, sporadic syndrome that causes progressive, patchy overgrowth, bony distortion or deformation, tumor predisposition, and mental retardation. The purpose of this project is to determine the natural history and etiology of Proteus syndrome. The natural history and the phenotypic range will be determined by clinical assessment and longitudinal follow-up of a cohort of patients. Very little is known about the natural history and the range of the phenotype of PS. The literature is awash with case reports of patients claimed to have PS who clearly do not meet diagnostic criteria. Some diagnostic confusion should be expected for patients affected by a disorder that is hypothesized to be due to somatic mosaicism, as this mosaicism is inherently variable among patients. To address this issue, we propose to accrue a cohort of patients with PS and overlapping phenotypes and follow them over time. As the disorder is usually apparent at or soon after birth and appears to evolve at least into the 20's, it will be necessary to have long-term follow-up. The etiology will be studied using various comparative molecular biology techniques including representational difference analysis, cDNA arrays, and other techniques.